The Ageing Epigenome: Preventing Old Genes from Learning New Tricks

I know, I know. You read the phrase “the ageing epigenome” and, apart from noticing that the spelling is un-American, you find that really only one thing springs to mind: There must be a lot of anagrams I could make from that phrase. My examples appear below, but feel free to play along at home. (For the uninitiated: Wikipedia describes an anagram as a type of wordplay, the result of rearranging the letters of a word or phrase to produce a new word or phrase, using all the original letters exactly once.)

(Teenage Me Going Hip) I suppose back in the day I should have guessed that someday I’d be looking at how genes switch on and off. That’s the simplest way of describing epigenetic regulation, and in retrospect it was the obvious career path for someone entering medical school in the West of Ireland.

(Age Eighteen Moping) A lesson to grumpy teenagers everywhere: you may end up working on something fun. You see, conceptually, epigenetic regulation of genes is kind of like coaching athletes to run certain plays. You have the same genes in every cell type, just as you have a finite number of players on the team. Just as you don’t want the chaos of having the players try every play simultaneously, you want only some genes switched on at a time. Running the play that makes a liver cell is quite different from running the play that makes a skin cell. The epigenome calls the plays, and the genes (which—dirty little secret—are not that smart) run the plays as they have been told to.

If you’re old enough to read this, most of the plays in your body have already been run—the more than 200 types of cells in the body were programmed epigenetically, and now they just need to keep on message. So when we start to think about what could possibly go wrong as we age, we think of two things. Might the epigenome’s program to maintain a liver cell’s instructions to remain a liver cell start to wobble a bit over time? And what if, during the frenetic period of programming and reprogramming the epigenome early in life, we were being buffeted by an odd diet, chemicals or other factors that jolted the programming slightly off track?

(Engage Hope Mite Gin) For example, ethanol, the fun ingredient in booze, has known effects on the epigenome when you expose it to cells being grown in a dish. Diet is being linked to epigenetic changes, as are exercise and stress: the list is expanding like an abscess.

(Heaping Teeming Ego) Clearly, as scientists, we are humble individuals and merely seek reward for our endeavors in terms of the insights gained. Fame and fortune are simply words that both begin with the letter F. So when I saw that a few Einstein investigators—including me—were mentioned earlier this year in National Geographic discussing age and the epigenome, my only instinct was that this was good for humankind.

(Ageing Meeting Hope) That’s because publicity goes hand in hand with what really counts in life: whether the National Institutes of Health (NIH) will throw some change into your cup. The fine people of the NIH, specifically those at the National Institute on Aging, held a productive meeting last summer to figure out how best to design studies to look at the effects of age on the epigenome.

(Heaping Meeting Ego) Everyone at these meetings tends to be very collegial and self-deprecating. The old joke that scientists would rather use each other’s toothbrushes than each other’s hypotheses? A cruel stereotype.

(Ageing Teeming Hope) But seriously, folks. There’s genuinely a lot of promise in this field of epigenomics as we try to understand aging, or even (transatlantic) ageing. We have drugs that target the epigenome in cancer; increasingly refined agents that nudge the epigenome back on track might be part of the treatment for age-related conditions. Epigenetic therapy might therefore allow better-quality and longer lives. I hope so—before I get too old myself.

John M. Greally, M.B.,B.Ch., Ph.D. is chief, Division of Computational Genetics at Albert Einstein College of Medicine. He is also a member of the Scientific and Clinical Steering Committee at New York Genome Center.